ClinVar Genomic variation as it relates to human health
NM_000152.5(GAA):c.1A>G (p.Met1Val)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000152.5(GAA):c.1A>G (p.Met1Val)
Variation ID: 188785 Accession: VCV000188785.17
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q25.3 17: 80104587 (GRCh38) [ NCBI UCSC ] 17: 78078386 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Mar 29, 2015 Feb 14, 2024 Jun 22, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000152.5:c.1A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000143.2:p.Met1Val missense initiator codon variant NM_001079803.3:c.1A>G NP_001073271.1:p.Met1Val missense initiator codon variant NM_001079804.3:c.1A>G NP_001073272.1:p.Met1Val missense initiator codon variant NC_000017.11:g.80104587A>G NC_000017.10:g.78078386A>G NG_009822.1:g.8032A>G LRG_673:g.8032A>G LRG_673t1:c.1A>G - Protein change
- M1V
- Other names
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- Canonical SPDI
- NC_000017.11:80104586:A:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00000
Trans-Omics for Precision Medicine (TOPMed) 0.00000
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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GAA | - | - |
GRCh38 GRCh38 GRCh37 |
2754 | 2807 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Jun 22, 2023 | RCV000169114.12 |
Submissions - Germline
Classification
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The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely pathogenic
(May 15, 2014)
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criteria provided, single submitter
Method: literature only
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Glycogen storage disease, type II
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000220316.3
First in ClinVar: Mar 29, 2015 Last updated: Sep 03, 2023 |
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Pathogenic
(Jun 22, 2023)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type II
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital
Accession: SCV003934925.2
First in ClinVar: Jun 24, 2023 Last updated: Sep 03, 2023 |
Comment:
The homozygous start loss variant c.1A>G (p.Met1?) has been identified in a proband with muscle weakness and hypotonia, . This variant has not been found … (more)
The homozygous start loss variant c.1A>G (p.Met1?) has been identified in a proband with muscle weakness and hypotonia, . This variant has not been found in gnomAD (aggregated) database. This has been previously reported PMID: 18429042 This homozygous variant start loss variant c.1A>G (p.Met1?) has been identified in 6 more patient and in 4 patient in heterozygous state. (less)
Sex: male
Ethnicity/Population group: South East Asian
Geographic origin: India
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Pathogenic
(May 05, 2022)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type II
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001207982.6
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys103 amino acid residue in GAA. Other variant(s) that disrupt this … (more)
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys103 amino acid residue in GAA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1109266, 14695532, 18429042, 18607768, 24158270, 29181627). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 188785). Disruption of the initiator codon has been observed in individuals with Pompe disease (PMID: 22252923, 29124014, 29422078). This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the GAA mRNA. The next in-frame methionine is located at codon 122. (less)
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Pathogenic
(Sep 08, 2021)
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no assertion criteria provided
Method: clinical testing
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Glycogen storage disease type II
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002091876.2
First in ClinVar: Apr 23, 2022 Last updated: Sep 03, 2023 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Long term clinical history of an Italian cohort of infantile onset Pompe disease treated with enzyme replacement therapy. | Parini R | Orphanet journal of rare diseases | 2018 | PMID: 29422078 |
Pompe disease in Austria: clinical, genetic and epidemiological aspects. | Löscher WN | Journal of neurology | 2018 | PMID: 29181627 |
A molecular analysis of the GAA gene and clinical spectrum in 38 patients with Pompe disease in Japan. | Fukuhara Y | Molecular genetics and metabolism reports | 2017 | PMID: 29124014 |
Extended phenotype description and new molecular findings in late onset glycogen storage disease type II: a northern Italy population study and review of the literature. | Remiche G | Journal of neurology | 2014 | PMID: 24158270 |
Predicting cross-reactive immunological material (CRIM) status in Pompe disease using GAA mutations: lessons learned from 10 years of clinical laboratory testing experience. | Bali DS | American journal of medical genetics. Part C, Seminars in medical genetics | 2012 | PMID: 22252923 |
Molecular diagnosis of German patients with late-onset glycogen storage disease type II. | Joshi PR | Journal of inherited metabolic disease | 2008 | PMID: 18607768 |
Molecular and functional characterization of eight novel GAA mutations in Italian infants with Pompe disease. | Pittis MG | Human mutation | 2008 | PMID: 18429042 |
Twenty-two novel mutations in the lysosomal alpha-glucosidase gene (GAA) underscore the genotype-phenotype correlation in glycogen storage disease type II. | Hermans MM | Human mutation | 2004 | PMID: 14695532 |
Moderate hypoxia exposure and fetal development. | Astrup P | Archives of environmental health | 1975 | PMID: 1109266 |
Text-mined citations for rs786204467 ...
HelpRecord last updated Feb 14, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.